Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.
|Original language||English (US)|
|Number of pages||8|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|State||Published - Jul 31 2009|
Bibliographical noteFunding Information:
L.J.N. is supported by The Ellison Medical Foundation (AG-NS-0303-05) and NIEHS (R01 ES016114). K.P. and A.D.D. were supported by NIH grant U19AI067751.
- Gene targeting
- Genome instability
- Interstrand crosslinks
- Mouse models
- Stem cells